Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor a (ERa). RIZ1 has previously been shown to be a specific ERa coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704+/- of a proline at position 704) to coactivate the ERa and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERa in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704+/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704+/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.

Objective: Bone mineral density (BMD) is under strong genetic control and a number of candidategenes have been associated with BMD. Both muscle strength and body weight are considered to beimportant predictors of BMD but far less is known about the genes affecting muscle strength andfat mass. The purpose of this study was to investigate the poly adenosine (A) repeat and the BsmISNP in the vitamin D receptor (VDR) in relation to muscle strength and body composition in healthywomen.

Design: A population-based study of 175 healthy women aged 20–39 years was used.

Conclusions: Genetic variation in the VDR is correlated with muscle strength, fat mass and bodyweight in premenopausal women. Further functional studies on the poly A microsatellite areneeded to elucidate whether this is the functionally relevant locus or if the polymorphism is in linkagedisequilibrium with a functional variant in a closely situated gene further downstream of the VDR30UTR.

Aims: Fallers and especially recurrent fallers are at high risk for injuries. The aim of this study was to evaluate fall epidemiology in older men with special attention to the influence of age, ethnicity and country of residence. Methods: 10,998 men aged 65 years or above recruited in Hong Kong, the United States (US) and Sweden were evaluated in a cross-sectional retrospective study design. Self-reported falls and fractures for the preceding 12 months were registered through questionnaires. Group comparisons were done by chi-square test or logistic regression. Results: The proportion of fallers among the total population was 16.5% in ages 65-69, 24.8% in ages 80-84 and 43.2% in ages above 90 (P <0.001). The corresponding proportions of recurrent fallers in the same age groups were 6.3%, 10.1% and 18.2%, respectively (P <0.001), and fallers with fractures 1.0%, 2.3% and 9.1%, respectively (P <0.001). The proportion of fallers was highest in the US, intermediate in Sweden and lowest in Hong Kong (in most age groups P <0.05). The proportion of fallers among white men in the US was higher than in white men in Sweden (all comparable age groups P <0.01) but there were no differences in the proportion of fallers in US men with different ethnicity. Conclusions: The proportion of fallers in older men is different in different countries, and data in this study corroborate with the view that society of residence influences fall prevalence more than ethnicity.

in comparison to both occasional fallers and non-fallers, recurrent fallers performed more poorly on all the physical ability tests (all P < 0.001). A score below -2 standard deviations (SDs) in the right-hand grip strength test was associated with an odds ratio of 2.4 (95% CI 1.7, 3.4) for having had recurrent falls compared with having had no fall and of 2.0 (95% CI 1.3, 3.4) for having had recurrent falls compared with having had an occasional fall.

CONCLUSION:

low performance in physical ability tests are in elderly men associated with recurrent falls.

BACKGROUND: Cruciate ligament ruptures and shoulder dislocations are often caused by trauma, but predisposing intrinsic factors might also influence the risk. These injuries are more common in those with a previously injured sibling, an observation that might indicate a genetic predisposition. It is well known that polymorphisms in the collagen I gene are associated not only with osteoporosis and osteoporotic fracture risk, but also with osteoarthritis.

HYPOTHESIS: Because collagen I is abundant in ligaments and tendons, the authors hypothesized that collagen I alpha1 Sp1 polymorphism also was related to the occurrence of cruciate ligament ruptures and shoulder dislocations.

STUDY DESIGN: Case-control study; Level of evidence, 3.

METHODS: A total of 358 patients and 325 randomly selected population-based female controls were included in the study. Of the cases, 233 had a cruciate ligament rupture and 126 had had a shoulder dislocation. Age-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) estimated by unconditional logistic regression were used as measures of association.

RESULTS: Compared with the homozygous SS category, the heterozygous participants displayed a similar risk (OR, 1.06; 95% CI, 0.76-1.49), whereas the ss genotype was underrepresented in the injured population compared with the controls (OR, 0.15; 95% CI, 0.03-0.68). This latter estimate was similar for both cruciate ligament ruptures and shoulder dislocations, and was furthermore not modified by general joint laxity.

CONCLUSION: The authors found a substantially decreased risk of these injuries associated with collagen type I alpha1 Sp1 polymorphism. The study might encourage other investigators to consider further research in the area of genes and soft tissue injuries.

Objective: In sports medicine, muscle strength and joint flexibility of the contralateral limb is used as a rehabilitation goal for the injured extremity. The present study was designed to determine whether side differences in hamstrings and quadriceps muscle strength, or in the ratio between hamstrings and quadriceps strength (H:Q), might be of clinical importance. Design: Cross-sectional study in a randomly selected, population-based cohort. Setting: University hospital in Uppsala. Quadriceps and hamstrings strength was assessed by maximum isokinetic concentric contractions at an angular velocity of 90 degrees/s. Participants: A sample of 159 randomly selected women from Uppsala county population registers, aged 20-39 years, was included in the study. Main outcome measures: Peak isokinetic concentric torques of the quadriceps and hamstrings, and the corresponding H:Q ratios. Results: In this cohort of non-athletes the muscle strength in the dominant leg was on average 8.6% (p 0.001) in the non-dominant leg. Conclusions: Our study shows that in a population-based sample of women there is a significant asymmetry in leg muscle strength favouring non-dominant leg flexion and dominant leg extension. In this study the H:Q ratio was therefore substantially lower in the dominant leg. Whether this should influence rehabilitation goals must be further investigated.

To evaluate if clinically usable estimates of physical performance and level of habitual physical activity are associated with fall risk in elderly men. A population-based sample of 3014 randomly selected men aged 69-80 years was recruited to medical centers in Gothenburg, Malmoe, or Uppsala. The level of physical activity and self-reported falls during the preceding 12 months was evaluated using a questionnaire. The physical performance ability was estimated by measurements of handgrip strength, a timed stands test, a 6-m walking test and a 20-cm narrow walk test. Falls were reported in 16.5% of the men. Fallers performed 6.2+/-19.0% (mean+/-standard deviations; S.D.) less in right handgrip measures, 8.8+/-40.6% slower in the timed stands test, 6.8+/-30.8% slower in the 6-m walking test, and 5.3+/-28.8% slower in the 20-cm narrow walk test (all p<0.001, respectively). The odds ratio for falls among men who performed <-3 S.D. or failed compared to the mean (+1 S.D. to -1 S.D.) in the timed stands test was 3.41 (95% CI 2.31-5.02; p<0.001) and 2.46 (95% CI 1.80-3.34; p<0.001) in 20-cm narrow walk test. There were more fallers that never were physical active (73.0% vs. 65.4%, p<0.001) and who were sitting more (6.4+/-2.5 h/day vs. 6.0+/-2.3 h/day, p<0.05) than among the non-fallers. Fallers scored less than non-fallers in all the estimates of physical performance and they were more sedentary in their life style. The report suggests that clinical usable tests of physical performance and evaluation of habitual physical activity in the clinical situation possibly can be used to predict risk of falls in elderly men.

Vertebral fractures (VFs) are the clinical consequence of spinal osteoporosis and may be associated with back pain and aggravated kyphosis. However, the relative importance of VFs as an underlying cause of kyphosis and chronic back pain is not known. The aim of this study was to investigate the relationship between prevalent VFs and the size of kyphosis, and back pain in osteoporotic women. Thirty-six women, aged 74.6 +/- 8.3 years, were consecutively recruited from the osteoporosis unit at Uppsala University Hospital. The patients had 1-9 radiographic verified VFs. Tragus wall distance (TWD) and numeric rating scale were used to measure kyphosis and pain. All patients had a hyperkyphosis (TWD >= 10 cm). Notably, there were no associations between numbers or location of VFs versus size of kyphosis (rho = 0.15, p = 0.4; rho = -0.27, p = 0.12) or severity of back pain (rho = -0.08, p = 0.66; rho = 0.16, p = 0.35). Furthermore, no association was evident between kyphosis and back pain (rho = -0.02, p = 0.89). There was, however, an association between size of kyphosis and age (R = 0.44, p = 0.008). In conclusion, these data suggest that prevalent VFs are not significantly associated with kyphosis or chronic back pain, in patients with manifest spinal osteoporosis.

The WHO criteria for osteoporosis are based on bone mineral density (BMD) values in comparison to a reference population of healthy young adults. The aim of this study was to create BMD references for ethnic Swedish women, and to investigate whether the use of these T-score measurements influence the amount of Swedish postmenopausal patients that are diagnosed as having osteoporosis. A bone density reference was created by measuring a population-based sample of 335 randomly selected Swedish women aged 20-39yr. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, proximal femur, and total body. These locally derived T-score values were subsequently used to diagnose a sample of 300 consecutive postmenopausal Swedish patients referred to the Uppsala Osteoporosis Unit. There was a slight age-dependent decrease in femoral neck BMD, whereas no age effect was seen at other sites such as total hip, lumbar spine, or total body. This suggests that the cohort represents the steady state BMD at the ages of expected peak bone mass in Swedish women. The correlation between BMD measures at different sites differed from r=0.55 (lumbar spine BMD vs femoral neck BMD [FNBMD]) to r=0.92 (total hip BMD vs FNBMD). Central DXA-generated T-scores were calculated from this cohort, and these were significantly higher (0.3-0.5 SD) as compared with manufacturers and NHANESIII reference populations. This indicates that young Swedish women have a higher peak bone mass than the subjects included in the reference populations currently used for clinical measurements. The T-score in total hip derived from the investigated cohort was subsequently used to diagnose 300 clinical patients (mean age 63yr) referred for a DXA scan by their physicians. The use of this locally established and ethnic representative, T-score reference increased the prevalence of osteoporosis in femoral neck and total hip with 53-106%. A Swedish female BMD reference representing peak bone mass has been established and the normative data are presented. Notably, this cohort has considerably higher BMD as compared to the NHANESIII and manufacturer's reference populations. The use of the present T-score reference therefore causes approximately a 2-fold increase in the amount of Swedish postmenopausal women that fulfill the WHO criteria for osteoporosis. This demonstrates the problems with using T-score as diagnostic threshold for osteoporosis and is an argument for future strategies to obtain standardized densitometric cut-offs, for example, mg/cm(2).

With aging, the incidence of falls and fractures increases. There has during the last decades been secular changes in demographics so that the proportion of elderly increases in society. Hence, there is an increasing need for clinicians to be able to make a solid appraisal of the elderly patient's functional capacity, as to identify individuals with an increased risk to fall. If high risk individuals could be targeted fall preventive strategies might be implemented in specific risk cohorts. This would require reference values for muscle strength tests and functional tests, in order to defined high risk individuals performing inferior. From the MrOS Sweden cohort, 999 subjects aged 70-80 years were evaluated. Muscle strength and functional performance was tested by timed-stands test, 6-m and 20-cm narrow walk tests and Jamar handgrip strength test. Normative data is presented. With increasing age, there was a 10-18% successively decline in performance throughout the entire age span. This study provides reference values for handgrip strength and functional muscle tests in 70-80 years old men. The decline in the test values with increasing age, infer the use of age-specific normative data when using these tests both in clinical and research settings.

OBJECTIVE:: More than 50% of all fractures occur in people without osteoporosis. Hormone therapy increases bone density, improves postural balance, and reduces fracture risk in postmenopausal women. It is unclear whether tibolone, a synthetic steroid hormone drug, can improve muscle strength. Thus, the aim of this study was to study the effects of low-dose tibolone therapy on muscle strength in older women. METHODS:: Eighty healthy women (69 completed the study) 60 years or older were recruited through advertising in the local media. They were randomly allocated to receive either tibolone 1.25 mg/day or placebo for 6 months. The stand-up test was used to assess leg muscle strength and balance. Handgrip and leg muscle strength were measured using JAMAR and modified Cybex dynamometers. RESULTS:: Baseline characteristics, including serum estradiol values and muscle strength, were similar in the two groups. Compliance with the therapy regimen was very high, averaging more than 97% in both groups. After 6 months, mean values for handgrip strength, knee extensor strength, and average time to perform 10 stands were improved numerically in both groups compared with values during baseline. However, there were no significant differences in these parameters within or between groups, and differences remained nonsignificant after adjustment for age, serum estradiol, and baseline value. CONCLUSIONS:: Short-term treatment with low-dose tibolone (1.25 mg/d) seems not to affect muscle strength in older women.

BACKGROUND: Osteoporosis is a growing health problem. One of the proposed reasons for this is a more sedentary lifestyle. The aim of this study was to investigate the associations between muscle strength and total body bone mineral density (TBMD) in young adults at expected peak bone mass. METHODS: Sixty-four women and 61 men (total 125) 21 years of age were included. Handgrip strength, isokinetic knee-flexion and -extension muscle strength, TBMD, and body composition were measured. RESULTS: Univariate regression analyses showed that knee flexion and extension explained almost 30% of the variation in TBMD in women, whereas handgrip strength was not associated with TBMD. In men, no correlation between any measures of muscle strength and TBMD was evident. Stepwise regression analysis showed that knee-flexion and -extension muscle strength in women were associated with TBMD, R2=0.27. In men, lean body mass, fat mass, weight, and height were predictors for TBMD, R2=0.43, whereas muscle strength did not affect the prediction of TBMD. CONCLUSIONS: Muscle strength at weight-bearing sites is related to TBMD in women, whereas body composition is related to TBMD in men. The association of lower limb strength on TBMD only in young women indicates a gender difference.